H2-Histamine Antagonist (Famotidine) Induced Adverse CNS Reactions with Long-Standing Secondary Mania and Epileptic Seizures

Abstract

We report on the case of a 65-year-old female who was treated for one week with famotidine, a reversible H(2)-histamine antagonist, due to gastric pain. Shortly after treatment began, she presented manic symptoms and developed two generalized seizures, after which famotidine was discontinued. Manic symptoms were present for three months; intermittent treatment with both carbamazepine and antipsychotic medication was necessary before her mental status was completely restored. While cimetidine and ranitidine are known to cause secondary mania, this symptom has not been described for famotidine. CNS side effects are usually short-lived and respond to discontinuation of the drug, which was not the case in our patient. During a follow-up period that has so far lasted four years, the patient has been stable without any psychiatric medication. Adjusting the maintenance dosage of H(2)-histamine antagonists has been recommended in elderly patients since age-related reduction in renal plasma flow, glomerular filtration rate and renal tubular function may be present, which can in turn elevate histamine levels in plasma and cerebrospinal fluid. Our patient, however, had normal renal function and was free of organic or psychiatric diseases, so what pathogenetic mechanism led to the remarkably long standing manic syndrome after a relatively short course of famotidine remained unknown; famotidine seems to cause the same spectrum of adverse central nervous system (CNS) reactions as other H(2)-histamine antagonists.

Effects of cimetidine-like drugs on recombinant GABAA receptors

“…Similar findings were reported in mice after administration of cimetidine; systemic administration of large doses resulted in tonic seizures (Amabeoku and Chikuni, 1993), whereas intracerebral administration produced both clonic and tonic seizures (Shimokawa et al, 1996). Even in humans, the H 2 antagonist famotidine has been reported a induce tonic-clonic seizures (von Einsiedel et al, 2002). Speculation has pointed to a role for GABAergic mechanisms (either directly or indirectly) in H 2 antagonist-induced seizures, but this has not been substantiated.…”

“…Several studies have reported the appearance of seizures after systemic or central administration of H 2 antagonists (Shimokawa et al, 1996;Gerald and Richter, 1976;Amabeoku and Chikuni, 1993;von Einsiedel et al, 2002). Gerald and Richter reported that systemic and intraventricular administration of the H 2 antagonist metiamide in mice increased the risk of pentylenetetrazol-induced tonic and clonic seizures, respectively (Gerald and Richter, 1976).…”

Efeitos colaterais da ranitidina aplicada em dose terapêutica em cães saudáveis

“…Os efeitos cardíacos dos antagonistas H 2 só são detectados em indivíduos em estado de choque (CHRUSCH et al, 1999), não havendo evidências de estímulo arritmogênico (UPRICHARD & HARRON, 1990) nem de alteração na pressão sanguínea em Ciência Rural, v.40, n.2, fev, 2010. pacientes saudáveis (MCCORD et al, 2006). Porém, há relatos de desenvolvimento de alterações em sistema nervoso central de seres humanos, como letargia, desorientação, sonolência e confusão, principalmente nos idosos ou em indivíduos com função renal diminuída (SLUGG et al, 1992;EINSIEDEL et al, 2002).…”

Famotidine-induced reversal of meperidine-related serotonin syndrome: a case report

“…Famotidine is a histamine receptor antagonist with high selectivity for histamine 2 (H2) receptors. It has been reported to be associated with several unexpected central nervous system (CNS) effects such as delirium, mania, and seizures [10]. Delirium associated with famotidine has been reported in several cases, possibly associated with central anticholinergic effects [11].…”